腺嘌呤诱导慢性肾功能衰竭并发心血管病变大鼠模型的分析  

A Rat Model of Adenine-induced Chronic Renal Failure Complicated with Cardiovascular Disease

作　　者：张圆圆 靳培培 李宛哲 郭登洲[2] ZHANG Yuanyuan;JIN Peipei;LI Wanzhe;GUO Dengzhou(Graduate School,Hebei University of Chinese Medicine,Shijiazhuang 050200,China;The First Affiliated Hospital of Hebei University of Chinese Medicine,Hebei Provincial Hospital of Traditional Chinese Medicine,Shijiazhuang 050011,China)

机构地区：[1]河北中医药大学研究生学院,石家庄050200 [2]河北中医药大学第一附属医院/河北省中医院,石家庄050011

出　　处：《中国实验方剂学杂志》2023年第16期79-88,共10页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：河北省中医药管理局科研计划项目(2023021);河北省自然科学基金项目(H2022423367);河北中医学院博士研究生创新项目(XCXZZBS2023009)。

摘　　要：目的:通过观察腺嘌呤灌胃不同时间对模型大鼠一般生命体征、生化指标、心肾组织结构及功能的影响,探讨腺嘌呤诱导慢性肾功能衰竭(CRF)并发心血管病变大鼠模型的制备方法。方法:模型组大鼠腺嘌呤150 mg·kg^(-1)·d^(-1)灌胃16周,正常组大鼠给予等体积0.5%羧甲基纤维素钠溶液灌胃。于第5、13、17周检测模型组及正常组大鼠24 h尿蛋白定量(24 h-UTP)、生化指标、心脏超声,心肾组织结构及功能变化;于第5周、13周检测模型组及正常组大鼠血压;每周记录大鼠体质量变化;每日观察大鼠一般情况。结果:(1)与正常组大鼠比较,模型组大鼠体质量明显减少(P<0.05);(2)与正常组大鼠比较,模型组大鼠尿量明显增多,13周时出现蛋白尿;(3)与正常组大鼠比较,模型组大鼠第5周开始甘油三酯(TG)、总胆固醇(TC)、肌酐(Cr)、尿素氮(BUN)、血钾、血磷差异具有统计学意义(P<0.05),第17周时尿酸明显升高(P<0.05);血钙降低(P<0.01);(4)与正常组大鼠比较,模型组大鼠第5周出现血压明显升高(P<0.05),并逐渐加重;(5)与正常组大鼠比较,模型组大鼠第5周左心室室壁厚度差异无统计学意义,第13周差异有统计学意义(P<0.05);(6)与正常组大鼠比较,模型组大鼠第5周肾脏出现纤维化,纤维化程度不断加重,第13周心血管周围出现明显纤维化;(7)与正常组大鼠比较,模型组大鼠近端小管上皮细胞内可见高密度菱形针状结晶不断增多,细胞膜完整性受损,细胞间距不断增加,溶酶体不断增多,线粒体增生、线粒体嵴和线粒体外膜致密变不断加重;(8)与正常组大鼠比较,模型组大鼠精神萎靡,活动量明显减少并蜷缩弓背,毛发枯燥,耳部及脚趾苍白,面颊肿胀,夜尿多,血液暗红且浓稠。结论:腺嘌呤150 mg·kg^(-1)·d^(-1)灌胃12周可制备大鼠CRF伴有心血管病变等并发症模型,可用于CRF及其心血管病变等并发症的防治研究;腺嘌呤诱导CRF大鼠�Objective:To explore the preparation method of a rat model of adenine-induced chronic renal failure complicated with cardiovascular disease by investigating the effect of different time points of adenine gastric lavage on general vital signs,biochemical indicators,and cardiac and renal tissue structure and function of model rats.Method:Rats in the model group were administered adenine at 150 mg·kg^(-1)·d^(-1) by gavage for 16 weeks,while those in the normal group were given an equal volume of 0.5%carboxymethyl cellulose sodium solution by gavage.At weeks 5,13,17,24-hour urinary protein quantification(24 h-UTP),biochemical indicators,cardiac ultrasound,and changes in cardiac and renal tissue structure and function were measured in both the model and normal groups.Blood pressure was measured at weeks 5 and 13 in both groups.Weekly changes in body weight were recorded,and general conditions of the rats were observed daily.Result:①Compared with the normal group,the model group showed a significant decrease in body weight(P<0.05).②Rats in the model group exhibited a significant increase in urine volume,and proteinuria appeared at week 13.③Compared with the normal group,the model group showed significant differences in triglyceride(TG),total cholesterol(TC),creatinine(Cr),blood urea nitrogen(BUN),blood potassium,and blood phosphorus at week 5(P<0.05),which increased gradually over time.At week 17,uric acid levels were significantly elevated(P<0.05),and blood calcium levels were reduced at the end of week 17(P<0.01).④Compared with the normal group,the model group showed a significant increase in blood pressure at week 5(P<0.05),which progressively worsened.⑤There was no statistically significant difference in left ventricular wall thickness between the model and normal groups at week 5,but a significant difference was observed at week 13(P<0.05).⑥Fibrosis appeared in the kidneys of rats in the model group at week 5 and gradually worsened,while obvious fibrosis occurred around the cardiovascular system at w

关 键 词：腺嘌呤 CRF 心血管损伤 脾肾阳虚、浊瘀阻滞 

分 类 号：R284[医药卫生—中药学] R285[医药卫生—中医学] R289R287R22R2-031R33R24